慢性炎症贯穿于动脉粥样硬化（AS）发病全过程，其诱导的细胞外基质弹性蛋白的弹性降解（EL）与弹性生成（EG）功能紊乱，是动脉结构重塑及弹性衰退的重要机制。我院确有疗效的名医验方滋肾清肝方（ZQF），前期研究表明其可干预AS动脉弹性衰退及肾脏细胞外基质EL功能。然而ZQF对EG功能紊乱的影响及机制目前仍尚不明确。大量体外研究显示，EG合成弹性蛋白的前体物质tropoelastin在正常动脉细胞外基质中含量极低；然而当动脉EG功能紊乱时，tropoelastin可在细胞外基质中及内皮细胞表面大量蓄积。这一特征使得靶向tropoelastin的超声分子成像在理论上可实现活体状态下实时评估动脉EG功能紊乱状态。故本课题拟借助P-SLex双靶向超声微泡结合分子生物学技术，在不同致病因素刺激的ApoE-/-小鼠AS模型上，在体探讨ZQF及其功效单元调控动脉细胞外基质EG功能紊乱干预AS发生发展的机制。

Chronic inflammation exist throughout the whole pathogenesis of atherosclerosis (AS), and it induced elastolysis (EL) and elastogenesis (EG) dysfunction of extracecellular matrix, which is the key mechanism of arterial structure remodeling and elastic recession. Zishen Qinggan Fang (ZQF) was a effective decoction established by our institution for years. Preliminary studies suggested that ZQF can affect AS arterial elasticity and renal extracellular matrix degradation. However, the effect and mechanism of ZQF on EG dysfunction are still unclear. Numerous studies in vitro have shown that tropoelastin, a precursor of EG synthetic elastin, is extremely low in the extracellular matrix of healthy arteries. However, tropoelastin can accumulate in the extracellular matrix and on the surface of endothelial cells with arterial EG dysfunction. This feature makes targeted tropoelastin molecular ultrasound imaging theoretically possible to real-time assess the EG dysfunction status of arteries in vivo. Therefore, this study intends to explore the mechanism of ZQF and its units regulating EG dysfunction in arterial extracellular matrix to intervene the occurrence and development of AS in vivo, on the ApoE-/- mice model stimulated by different pathogenic factors, and by using P-SLex double-targeted ultrasound microbubbles combined with molecular biology technology. It is expected that this study will elucidate the molecular mechanism of effective ZQF in improving the decline of arterial elasticity from the perspective of molecular imaging, and provide a new theoretical basis for the treatment of AS with traditional Chinese medicine.